Scientists at the March of Dimes Prematurity Research Center (PRC) at Imperial College London have shown that both the good vaginal bacteria that protects against preterm birth and the bad bacteria that promotes it compete for the same sugar receptors inside the pregnant woman’s vagina, engaging in a power struggle that researchers hope can be tipped in favor of the good bacteria to avert early labor and a host of other gynecological health challenges.
The finding, detailed in a recent Nature Communications paper, sets the stage for attempts to alter the conditions inside the vaginal microbiome—which refers to the collection of bacteria, fungi, and viruses inside the vaginal canal—in ways that weaken the bad bacteria and strengthen the good, allowing them to colonize the vagina.
After the PRC scientists determine how both good and bad bacteria use the host sugars to adhere to and colonize the vagina, they have their sights set on a new experiment: creating a hostile environment for bad bacteria by lowering the pH inside the vaginal microbiome. A vaginal canal low in pH contains high levels of lactic acid, which, with its anti-inflammatory properties, is detrimental to bad bacteria but advantageous to good, giving them the upper hand in the fight for dominance.
“This research helped us prove what we have predicted for a long time: that both good and bad bacteria are knocking on the same doors inside the vaginal canal, each looking to colonize the vaginal microbiome through these openings,” said study first author Dr. Virginia Tajadura-Ortega, a sugar researcher at the Imperial PRC.
“In the future, we hope to show that by lowering the pH in the vagina and restoring populations of the good bacteria Lactobacillus crispatus, we cannot only help overpower the bad bacteria for the receptor sites, but also colonize the vagina with the good bacteria to achieve protection against preterm birth and other adverse outcomes.”
In addition to Dr. Tajadura-Ortega, the paper’s two other key researchers, both joint senior authors, were Imperial PRC scientists Dr. Yan Liu, the head of Imperial’s carbohydrate microarray facility, and Dr. David MacIntyre, a co-director of the March of Dimes center.
As part of the paper, the team developed a novel glycan microarray technology to be used as a new screening method to study whole bacterial cells at a large scale. By studying whole cells instead of just the proteins from bacterial cells they could study previously (called adhesins), the team was able to identify which sugars (found on vaginal cells and proteins) those invader bacterial cells attached to.
“This broader approach allowed us to capture sugar-binding interactions that may be missed when only studying individual bacterial proteins,” said Dr. Liu.
The team found that one family of sugars, called chondroitin sulphates, which are found on vaginal epithelial cells, are key targets for both the good bacteria, the most beneficial of which is Lactobacillus crispatus, and the bad bacteria, which includes Gardnerella vaginalis and Group B Streptococcus. This crucial finding makes the sugar a vital focus of future study.
Since the good L. crispatus bacteria promotes an anti-inflammatory environment in the vagina, its beneficial role extends past preterm birth prevention and into protection against Human Papillomavirus (HPV), sexually transmitted infections (STIs), bacterial vaginosis, and more.
Discovering which sugars are targeted by bacteria as entry points into the microbiome allows researchers to stack the deck in favor of good bacteria, Dr. MacIntyre said, with the potential to offer protection against a host of adverse outcomes for pregnant and non-pregnant women.
“Understanding how these sugars enable bugs to get a foothold in the vaginal microbiome offers new, exciting targets for therapeutic strategies designed to prevent or encourage their binding and colonisation,” he said.
Another future extension of this work involves uncovering the ways in which different bacteria modify the sugars they adhere to, and what effect those modifications have on reproductive health, said Dr. Tajadura-Ortega. For example, one of the ways in which bad bacteria displace good bacteria in the power struggle to adhere to the host’s cells is by deploying proteins to cleave, or cut, the sugar structure it adheres to, potentially preventing good bacteria from adhering to the same structure and even creating new attachment sites for bad bacteria.
Also, by studying the conditions that allow good and bad bacteria to thrive, Dr. Tajadura-Ortega said, the PRC team may be able to fine-tune vaginal probiotic recipes that may be commercially available for women in the next decade or so.
While there is currently no clinically proven vaginal supplement available for the prevention of preterm birth, Imperial PRC co-director Dr. Phillip Bennet is currently in the middle of a historic Randomized Controlled Trial (RCT) testing the efficacy of an L. crispatus probiotic called Lactin-V for the prevention of preterm birth. In parallel, other Imperial PRC researchers are working on studying the L. crispatus family of strains to determine which strain offers the most protection against inflammation—the gateway event to adverse outcomes in the reproductive tract—with the hopes of making it clinically available.
“Ultimately, we’re hoping our work can influence the formulation of an ideal vaginal probiotic for the prevention of preterm birth,” said Dr. Tajadura-Ortega. “One that will work for the vast majority of women, including those who resist L. crispatus long term colonization.”